本篇研究在調查口腔鱗狀細胞癌患者手術(腫瘤切除與頸淋巴清除)後，接受放射線化學治療，對其頸總動脈內膜中層厚度以及耳下腺的短期效果。我們在一區域教學醫院針對52例新診斷口腔癌患者，其中25員患者，接受腫瘤切除，頸淋巴廓清術和術後同步放射化學治療（CCRT），另外27員患者只接受腫瘤切除，頸淋巴廓清術；兩組共同進行前瞻性觀察研究追蹤共9個月。我們使用超音波來評估其頸總動脈內膜中層厚度評估加上B模式多普勒模式量測血管流速。頸總動脈內膜中層厚度測量結果方面，我們總共完成9個月的追蹤，共52員患者；25例實驗組術前與27例對照組相比，無顯著差異，兩組共同追蹤了9個月後發現實驗組的患者在接受手術與放射線治療後六個月，頸總動脈內膜中層厚度增厚有顯著意義（p<0.001），然而在對照組卻看不到此種現象，至於在B模式多普勒模式量測血管流速方面，兩組在追蹤9個月後並未發現有顯著性的改變。至於在耳下腺體研究結果方面，我們總共追蹤9個月，完成20例實驗組追蹤，追蹤九個月後，在口乾問卷方面，其口乾的生活品質明顯下降，在刺激性唾液分泌量則有顯著減少，而在耳下腺超音波影像分析則發現耳下腺組織結構有明顯的變化。本研究顯示，口腔癌患者接受手術與放射線後9個月，頸總動脈內膜中層厚度增加，可能會出現血管的病變；在超音波底下的耳下腺結構與組織也會產生變化，我們發現耳下腺體發炎、水腫以及纖維化。更重要的是，口腔癌患者如果有接受放射線治療，監控頸總動脈內膜中層厚度，加速動脈粥樣硬化的頸動脈成像生物標記物，可作為預測未來腦血管或心血管疾病發生的機率，並做早期預防。

Objective
To study the short-term effect of concurrent chemoradiation therapy (CCRT) on common carotid artery intima-media thickness (CCA-IMT) and parotid glands in post-operative patients with oral squamous cell carcinoma (OSCC).
Methods
We recruited 52 patients diagnosed with OSCC in this prospective study, of which 25 underwent CCRT (the CCRT group) and 27 did not undergo CCRT (the control group). The follow-up period for these 52 patients was approximately 9 months. We investigated the CCA-IMT and color Doppler flow imaging of the CCA in all patients by using B-mode Doppler ultrasonography on both the left and right common carotid arteries. We employed a computer program to measure the IMT of the mid-CCA posterior wall at the baseline and 9 months after patients received CCRT. We also evaluated the ultrasonographic features of the parotid glands by using echo-intensity histograms to assess the echogenicity, homogeneity, and heterogeneity of the parotid glands in the 20 OSCC patients of the CCRT group.
Measurements and results
Among the 52 OSCC patients recruited, we observed non-significant differences in age, sex, BMI, and other existing co-morbidities between the CCRT group (25 participants) and the control group (27 participants). For the CCRT group, the CCA-IMT at the baseline and 6 months after the patients received parotid-sparing intensity-modulated radiotherapy (IMRT) were 637 ± 131 µm and 733 ± 167 µm, respectively, for the left side (P < .001) and 639 ± 118 µm and 745 ± 149 µm, respectively, for the right side (P < .001). For the control group, the CCA-IMT data at the baseline and at 9 months were 614 ± 106 µm and 620 ± 109 µm for the left side (P = .087) and 595 ± 93 µm and 601 ± 95 µm for the right side (P = .110), respectively. The CCA-IMT was significantly thicker 6 months after IMRT began in the CCRT group. However, Doppler ultrasonographic velocity measurements in the CCA showed no significant difference between the baseline and 9 months in both the CCRT and non-CCRT groups. Compared with the baseline, xerostomia and the stimulated salivary rate decreased after 20 OSCC patients received radiotherapy for 9 months. We observed significant differences (P < .001) in 3 ultrasonographic histogram features in the 40 irradiated parotid glands.
Conclusions
We demonstrated that increased CCA-IMT in OSCC patients could occur as early as 6 months following IMRT. Monitoring the CCA-IMT as an imaging biomarker for predicting the possibility of cerebrovascular disease or the risk of accelerated atherosclerosis in carotid arteries is necessary. We also observed deteriorated xerostomia-related QOL scores and the altered morphologic and structural changes of the parotid glands, with ultrasonography, 6 months after the patients received head and neck IMRT.

Abayomi, O. K. (2004) Neck irradiation, carotid injury and its consequences. Oral Oncol, 40, 872-8.
Amato, M., P. Montorsi, A. Ravani, E. Oldani, S. Galli, P. M. Ravagnani, E. Tremoli & D. Baldassarre (2007) Carotid intima-media thickness by B-mode ultrasound as surrogate of coronary atherosclerosis: correlation with quantitative coronary angiography and coronary intravascular ultrasound findings. European heart journal, 28, 2094-101.
Bekiroglu, F., N. Ghazali, R. Laycock, C. Katre, D. Lowe & S. N. Rogers (2011) Adjuvant radiotherapy and health-related quality of life of patients at intermediate risk of recurrence following primary surgery for oral squamous cell carcinoma. Oral oncology, 47, 967-73.
Bilora, F., F. Pietrogrande, E. Campagnolo, A. Rossato, G. Polato, F. Pomerri & P. C. Muzzio (2010) Are Hodgkin and non-Hodgkin patients at a greater risk of atherosclerosis? A follow-up of 3 years. European journal of cancer care, 19, 417-9.
Blanco, A. I., K. S. Chao, I. El Naqa, G. E. Franklin, K. Zakarian, M. Vicic & J. O. Deasy (2005) Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys, 62, 1055-69.
Brennan, P. A., M. K. Herd, D. C. Howlett, D. Gibson & R. S. Oeppen (2012) Is ultrasound alone sufficient for imaging superficial lobe benign parotid tumours before surgery? Br J Oral Maxillofac Surg, 50, 333-7.
Chambers, M. S., A. S. Garden, D. Rosenthal, A. Ahamad, D. L. Schwartz, A. I. Blanco, K. S. Chao, W. H. Morrison, K. K. Ang & R. S. Weber (2005) Intensity-modulated radiotherapy: is xerostomia still prevalent? Curr Oncol Rep, 7, 131-6.
Chang, Y. J., T. C. Chang, T. H. Lee & S. J. Ryu (2009) Predictors of carotid artery stenosis after radiotherapy for head and neck cancers. Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter, 50, 280-5.
Chao, K. S., J. O. Deasy, J. Markman, J. Haynie, C. A. Perez, J. A. Purdy & D. A. Low (2001) A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results. Int J Radiat Oncol Biol Phys, 49, 907-16.
Chargari, C. (2013) The Issue of Radiation-induced Cardiovascular Toxicity: Preclinical Highlights and Perspectives on Preventive Strategies. Biomed J, 36, 150-151.
Cheng, S. C., M. T. Ying, D. L. Kwong & V. W. Wu (2011) Sonographic appearance of parotid glands in patients treated with intensity-modulated radiotherapy or conventional radiotherapy for nasopharyngeal carcinoma. Ultrasound Med Biol, 37, 220-30.
Cheng, S. W., A. C. Ting, P. Ho & L. L. Wu (2004) Accelerated progression of carotid stenosis in patients with previous external neck irradiation. Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter, 39, 409-15.
Chiba, I. (2001) Prevention of Betel Quid Chewers' Oral Cancer in the Asian-Pacific Area. Asian Pac J Cancer Prev, 2, 263-269.
Chu, C. N., S. W. Chen, L. Y. Bai, C. H. Mou, C. Y. Hsu & F. C. Sung (2011) Increase in stroke risk in patients with head and neck cancer: a retrospective cohort study. British journal of cancer, 105, 1419-23.
Crary, M. A., G. D. Mann & M. E. Groher (2005) Initial psychometric assessment of a functional oral intake scale for dysphagia in stroke patients. Arch Phys Med Rehabil, 86, 1516-20.
Deasy, J. O., V. Moiseenko, L. Marks, K. S. Chao, J. Nam & A. Eisbruch (2010) Radiotherapy dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys, 76, S58-63.
Dorresteijn, L. D., A. C. Kappelle, N. M. Scholz, M. Munneke, J. T. Scholma, A. J. Balm, H. Bartelink & W. Boogerd (2005) Increased carotid wall thickening after radiotherapy on the neck. European journal of cancer (Oxford, England : 1990), 41, 1026-30.
Eisbruch, A., H. M. Kim, J. E. Terrell, L. H. Marsh, L. A. Dawson & J. A. Ship (2001) Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer. Int J Radiat Oncol Biol Phys, 50, 695-704.
Etgen, T., G. Weidenhofer & T. Kubin (2009) Cisplatin-associated occlusion of the internal carotid artery. Onkologie, 32, 754-7.
Fasunla, A. J., B. H. Greene, N. Timmesfeld, S. Wiegand, J. A. Werner & A. M. Sesterhenn (2011) A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck. Oral Oncol, 47, 320-4.
Faul, F., E. Erdfelder, A. Buchner & A. G. Lang (2009) Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods, 41, 1149-60.
Faul, F., E. Erdfelder, A. G. Lang & A. Buchner (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods, 39, 175-91.
Fernandez Dominguez, J., R. Garcia Rodriguez, M. Valle Pereda & V. Mateos Marcos (2012) [Cerebral infarction after cisplatin-gemcitabine chemotherapy: probable cause-effect]. Neurologia, 27, 245-7.
Gianicolo, M. E., E. A. Gianicolo, F. Tramacere, M. G. Andreassi & M. Portaluri (2010) Effects of external irradiation of the neck region on intima media thickness of the common carotid artery. Cardiovascular ultrasound, 8, 8.
Greco, A., A. Gallo, A. De Virgilio, C. Marinelli, G. F. Macri, M. Fusconi, G. Pagliuca & M. de Vincentiis (2012) Carotid stenosis after adjuvant cervical radiotherapy in patients with head and neck cancers: a prospective controlled study. Clin Otolaryngol, 37, 376-81.
Holt, A., D. Van Gestel, M. P. Arends, E. W. Korevaar, D. Schuring, M. C. Kunze-Busch, R. J. Louwe & C. van Vliet-Vroegindeweij (2013) Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study. Radiat Oncol, 8, 26.
Howlett, D. C. (2003) High resolution ultrasound assessment of the parotid gland. Br J Radiol, 76, 271-7.
Huang, Y. S., C. C. Lee, T. S. Chang, H. C. Ho, Y. C. Su, S. K. Hung, M. S. Lee, P. Chou, Y. H. Chang & C. C. Lee (2011) Increased risk of stroke in young head and neck cancer patients treated with radiotherapy or chemotherapy. Oral oncology, 47, 1092-7.
Liao, K. A., Y. G. Tsay, L. C. Huang, H. Y. Huang, C. F. Li & T. F. Wu (2011) Search for the tumor-associated proteins of oral squamous cell carcinoma collected in Taiwan using proteomics strategy. J Proteome Res, 10, 2347-58.
Liu, S. Y., C. L. Lu, C. T. Chiou, C. Y. Yen, G. A. Liaw, Y. C. Chen, Y. C. Liu & W. F. Chiang (2010) Surgical outcomes and prognostic factors of oral cancer associated with betel quid chewing and tobacco smoking in Taiwan. Oral Oncol, 46, 276-82.
Martin, J. D., A. R. Buckley, D. Graeb, B. Walman, A. Salvian & J. H. Hay (2005a) Carotid artery stenosis in asymptomatic patients who have received unilateral head-and-neck irradiation. International journal of radiation oncology, biology, physics, 63, 1197-205.
--- (2005b) Carotid artery stenosis in asymptomatic patients who have received unilateral head-and-neck irradiation. Int J Radiat Oncol Biol Phys, 63, 1197-205.
Milliat, F., A. Francois, M. Isoir, E. Deutsch, R. Tamarat, G. Tarlet, A. Atfi, P. Validire, J. Bourhis, J. C. Sabourin & M. Benderitter (2006) Influence of endothelial cells on vascular smooth muscle cells phenotype after irradiation: implication in radiation-induced vascular damages. Am J Pathol, 169, 1484-95.
Nambi, V., L. Chambless, M. He, A. R. Folsom, T. Mosley, E. Boerwinkle & C. M. Ballantyne (2012) Common carotid artery intima-media thickness is as good as carotid intima-media thickness of all carotid artery segments in improving prediction of coronary heart disease risk in the Atherosclerosis Risk in Communities (ARIC) study. Eur Heart J, 33, 183-90.
Newton, H. B. (2012) Neurological complications of chemotherapy to the central nervous system. Handb Clin Neurol, 105, 903-16.
Nohara, R., H. Daida, M. Hata, K. Kaku, R. Kawamori, J. Kishimoto, M. Kurabayashi, I. Masuda, I. Sakuma, T. Yamazaki, H. Yokoi, M. C. I. N. C. J. Yoshida & Pmid (2012) Effect of intensive lipid-lowering therapy with rosuvastatin on progression of carotid intima-media thickness in Japanese patients: Justification for Atherosclerosis Regression Treatment (JART) study. Circulation journal : official journal of the Japanese Circulation Society, 76, 221-9.
Ntaios, G., C. Savopoulos, D. Karamitsos, I. Economou, E. Destanis, I. Chryssogonidis, I. Pidonia, P. Zebekakis, C. Polatides, M. Sion, D. Grekas & A. Hatzitolios (2010) The effect of folic acid supplementation on carotid intima-media thickness in patients with cardiovascular risk: a randomized, placebo-controlled trial. International journal of cardiology, 143, 16-9.
Periard, D., C. M. Boulanger, S. Eyer, N. Amabile, P. Pugin, C. Gerschheimer, D. C. I. N. I. M. J. J. Hayoz & Pmid (2007) Are circulating endothelial-derived and platelet-derived microparticles a pathogenic factor in the cisplatin-induced stroke? Stroke; a journal of cerebral circulation, 38, 1636-8.
Peszynska-Piorun, M., J. Malicki & W. Golusinski (2012) Doses in organs at risk during head and neck radiotherapy using IMRT and 3D-CRT. Radiol Oncol, 46, 328-36.
Powitzky, R., N. Vasan, G. Krempl & J. Medina (2010) Carotid blowout in patients with head and neck cancer. Ann Otol Rhinol Laryngol, 119, 476-84.
Putz, M. & F. Wenz (2012) Current strategies in radiotherapy of head and neck cancer. GMS Curr Top Otorhinolaryngol Head Neck Surg, 11, Doc02.
Rabin, B. M., J. R. Meyer, J. W. Berlin, M. H. Marymount, P. S. Palka & E. J. Russell (1996) Radiation-induced changes in the central nervous system and head and neck. Radiographics, 16, 1055-72.
Radfar, L. & D. A. Sirois (2003) Structural and functional injury in minipig salivary glands following fractionated exposure to 70 Gy of ionizing radiation: an animal model for human radiation-induced salivary gland injury. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 96, 267-74.
Scully, C. & J. Bagan (2009) Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis, 15, 388-99.
Shai, E., S. Siegal, Z. Michael, K. Itzhak, R. Ronen, M. Dror, B. Sylvia, B. H. Adina, A. H. Ramzia, F. Marina, C. Angela, Y. Dov, W. Joshua & B. Arie (2009) Carotid atherosclerotic disease following childhood scalp irradiation. Atherosclerosis, 204, 556-60.
Shariat, M., N. A. Alias & B. M. Biswal (2008) Radiation effects on the intima-media thickness of the common carotid artery in post-radiotherapy patients with head and neck malignancy. Postgraduate medical journal, 84, 609-12.
Shaw, R. J., A. Pace-Balzan & C. Butterworth (2011) Contemporary clinical management of oral squamous cell carcinoma. Periodontology 2000, 57, 89-101.
So, N. M., W. W. Lam, P. Chook, K. S. Woo, K. H. Liu, S. F. Leung, K. S. Wong & C. Metreweli (2002) Carotid intima-media thickness in patients with head and neck irradiation for the treatment of nasopharyngeal carcinoma. Clin Radiol, 57, 600-3.
Staffurth, J. (2010) A review of the clinical evidence for intensity-modulated radiotherapy. Clin Oncol (R Coll Radiol), 22, 643-57.
Teymoortash, A., N. Simolka, C. Schrader, M. Tiemann & J. A. Werner (2005) Lymphocyte subsets in irradiation-induced sialadenitis of the submandibular gland. Histopathology, 47, 493-500.
Thompson, S. K., J. G. McKinnon & W. A. Ghali (2003) Perioperative stroke occurring in patients who undergo neck dissection for head and neck cancer: unanswered questions. Canadian journal of surgery. Journal canadien de chirurgie, 46, 332-4.
Wada, A., N. Uchida, M. Yokokawa, T. Yoshizako & H. Kitagaki (2009) Radiation-induced xerostomia: objective evaluation of salivary gland injury using MR sialography. AJNR Am J Neuroradiol, 30, 53-8.
Warnakulasuriya, S. (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol, 45, 309-16.
Yang, X., S. Tridandapani, J. J. Beitler, D. S. Yu, E. J. Yoshida, W. J. Curran & T. Liu (2012a) Ultrasound Histogram Assessment of Parotid Gland Injury Following Head-and-Neck Radiotherapy: A Feasibility Study. Ultrasound in Medicine & Biology, 38, 1514-1521.
Yang, X., S. Tridandapani, J. J. Beitler, D. S. Yu, E. J. Yoshida, W. J. Curran & T. Liu (2012b) Ultrasound histogram assessment of parotid gland injury following head-and-neck radiotherapy: a feasibility study. Ultrasound Med Biol, 38, 1514-21.